A 31-year follow-up of those with occult spinal dysraphism, who underwent spinal cord untethering: Lower urinary tract function, skin stigmata, fertility, and work participation.

OBJECTIVES: This study evaluated patients with occult spinal dysraphism who underwent spinal cord untethering. METHODS: Twenty-four patients who visited us between 1983 and 2000 were followed-up for a mean duration of 31 years. We studied their lower urinary tract function, skin stigmata, fertility, and work participation. RESULTS: Questionnaires sent in 2022 revealed that 5 patients had normal voiding (Group A) and 19 patients had abnormal voiding (Group B). Groups A and B underwent spinal cord untethering at a mean age of 5.7 and 13.0 years, respectively, showing a significant statistical difference (p = 0.036). After spinal cord untethering, the number of patients with detrusor normoactivity increased from 0 to 5, i.e., 3 of 6 with detrusor overactivity (50%), 1 of 2 not examined, and 1 of 5 not known. Patients with detrusor underactivity also increased from 11 to 19. Severity of incontinence in the International Consultation on Incontinence Questionnaire-Short Form resulted in a mean value of 2.4 in Group A, which was significantly superior to the mean value of 9.1 in Group B (p = 0.004). Fourteen patients (58.3%) were married and had 21 healthy children. A majority of patients have had full-time jobs. A variety of skin stigmata were present in the lumbosacral region, and changes in vesico-urethral configurations were observed during a video-urodynamic study. CONCLUSIONS: Our study identified that the early timing of spinal cord untethering performed in neonates or infants and detrusor overactivity prior to untethering surgery are important factors in achieving normal bladder function.

Real prevalence of neural tube defects in Japan: How many of such pregnancies have been terminated?

The vital role of folic acid is to reduce the risk of having a neonate afflicted with neural tube defects. The prevalence of neural tube defects (myelomeningocele and anencephaly) has been reported in an incomplete form over the last 40 years in Japan. We aimed to evaluate the total number of neural tube defects including those delivered or terminated, to clarify the proportion of those terminated, and to internationally compare their prevalence. Through information on >311 000 deliveries obtained from 262 hospitals/clinics for 2 years of 2014 and 2015, we identified that the rate of total neural tube defects (termination of pregnancy, live births and stillbirths) was 8.29 per 10 000 deliveries for the year 2014 and was 8.72 for 2015, which were 1.5 and 1.6 times higher than the respective values (live births and stillbirths) reported. It is also observed that the ratio of the total number of myelomeningocele (termination of pregnancy, live births, and stillbirths) to that of anencephaly was approximately 1:1.2, that a half of pregnancies afflicted with neural tube defects were terminated, and that the proportion of termination of pregnancy due to myelomeningocele and due to anencephaly was 20% and 80%, respectively. Internationally, the real prevalence of neural tube defects in Japan was comparatively high, ranking fifth among the seven developed countries. In conclusion, the real prevalence of total neural tube defects was approximately 1.5 times higher than that currently reported by the Japan Association of Obstetricians and Gynecologists.

Survey on awareness of folic acid recognition and intake by female students.

To reduce the risk of neural tube defects, studies have been conducted on female students of medical services, nutritional science, and nursery education that investigated the awareness of folic acid by using questionnaires. Many investigators have suggested the need to provide detailed information about the awareness of folic acid and knowledge about folic acid intake and neural tube defect risk reduction. The dietary habits of female students showed a positive correlation with their estimated folic acid intake, suggesting that improvements in dietary habits are associated with the consumption of folic acid. The importance of folic acid intake must be more aggressively promoted among female students. Thus, many learning opportunities should be provided for such students to help increase their folic acid intake.

Neural tube defects: Risk factors and preventive measures.

For the last 25 years, it has been proven that the occurrence or recurrence of neural tube defects can be prevented with the administration of folic acid before and early pregnancy. At present, over 80 countries in the world, except Japan, have mandated the fortification of wheat flour and/or rice with folic acid, which has resulted in a significant reduction in the prevalence of neural tube defects. In 2000, the Japanese government recommended folic acid 400 µg daily for young women of childbearing age and women who are planning to conceive. In 2002, the government started to present information about the importance of folic acid in the development of fetuses in the Mother-Child Health Booklet annually. Despite these endeavors, the prevalence of neural tube defects has remained unchanged. We discuss the risk factors of neural tube defects and propose preventive measures to decrease the number of neonates with neural tube defects. We believe that the government should implement the fortification of staple food with folic acid very soon, which will eventually decrease not only the neonatal mortality and morbidity, but also the economic burden on our health care system.

Awareness of folic acid use increases its consumption, and reduces the risk of spina bifida.

The majority of neural tube defects were believed to be folic acid (FA)-preventable in the 1990s. The Japanese government recommended women planning pregnancy to take FA supplements of 400 µg/d in 2000, but the incidence of spina bifida has not decreased. We aimed to evaluate the OR of having an infant with spina bifida for women who periconceptionally took FA supplements and the association between an increase in supplement use and possible promoters for the increase. This is a case-control study which used 360 case women who gave birth to newborns afflicted with spina bifida, and 2333 control women who gave birth to healthy newborns during the first 12 years of this century. They were divided into two 6-year periods; from 2001 to 2006 and from 2007 to 2012. Logistic regression analyses were conducted to compute OR between cases and controls. The adjusted OR of having an infant with spina bifida for supplement users was 0.48 in the first period, and 0.53 in the second period. The proportion of women who periconceptionally consumed supplements significantly increased from 10 % in the first period to 30 % in the second period. Awareness of the preventive role of FA was a promoter for an increase in supplement use, and thus an FA campaign in high school seems rational and effective. The failure of the current public health policy is responsible for an epidemic of spina bifida. Mandatory food fortification with FA is urgent and long overdue in Japan.

C677T mutation in methylenetetrahydrofolate reductase gene and neural tube defects: should Japanese women undergo gene screening before pregnancy?

We analyzed the role of maternal C677T mutation in methylenetetrahydrofolate reductase (MTHFR) gene on spina bifida development in newborns. A total of 115 mothers who had given birth to a spina bifida child (SB mothers) gave 10 mL of blood together with written informed consent. The genotype distribution of C677T mutation was assessed and compared with that of the 4517 control individuals. The prevalence of the homozygous genotype (TT) among SB mothers was not significantly different from that among the controls (odds ratio [OR] = 0.65; 95% confidence interval [CI] = 0.31-1.25; P = 0.182), suggesting that MTHFR 677TT genotype in Japan is not associated with spina bifida development in newborns. The T allele frequency was not increased in SB mothers (34.8%) as compared to that of the control individuals (38.2%). Further, the internationally reported association between the two groups was found to be similar in all 15 countries studied except the Netherlands, where the TT genotype was found to be a genetic risk factor for spina bifida. For the prevention of affected pregnancy every woman planning to conceive has to take folic acid supplements 400 µg a day and the government is asked to take action in implementing food fortification with folic acid in the near future. In conclusion, it is not necessary for Japanese women to undergo genetic screening C677T mutation of the MTHFR gene as a predictive marker for spina bifida prior to pregnancy, because the TT genotype is not a risk factor for having an affected infant.

Risk factors for the occurrence of spina bifida (a case-control study) and the prevalence rate of spina bifida in Japan.

BACKGROUND: The Japanese government recommended in 2000 that women planning pregnancy should take 400 µg of folic acid daily to decrease the risk of having an infant with spina bifida. We aimed to identify risk factors for the occurrence of spina bifida and to evaluate how the prevalence rate has altered over the past 3 decades. METHODS: Subjects comprised 360 women who gave birth to spina bifida-affected offspring and 2333 women who gave birth to offspring without spina bifida between 2001 and 2012. A self-administered questionnaire was used to collect data, which were analyzed by multiple logistic regression models. The prevalence rate of spina bifida was obtained through data provided by international and domestic organizations. RESULTS: Four variables were significantly associated with the increased risk of having newborns afflicted with spina bifida: not taking folic acid supplements (odds ratios [OR], 2.50; 95% confidence interval [CI], 1.72-3.64), presence of spina bifida patients within third-degree relatives (OR, 4.26; 95% CI, 1.12-16.19), taking anti-epileptic drugs without folic acid (OR, 20·20; 95% CI, 2.06-198.17), and low birth weight in the newborns ≤ 2500 g (OR, 4.21; 95% CI, 3.18-5.59). The prevalence rate of spina bifida has remained 5 to 6 per 10,000 total births and has not shown any decreasing trend over the past 11 years. CONCLUSION: Four risk factors were identified among Japanese women. Because recommendations and information have not decreased the occurrence of spina bifida, the Japanese government should implement mandatory food fortification.

[Changes in life styles of pregnant women and risks for having a pregnancy afflicted with spina bifida].

AIMS: Though periconceptional intakes of folic acid could prevent the occurrence of spina bifida by 50 to 70%, the prevalence has not shown any decreasing tendency during the past 30 years in Japan. We aim to analyze various parameters through life style questionnaires and 3-day food records obtained from pregnant women the last 10 years, and to examine whether their life styles have been shifting to the direction of lowering the incidence of spina bifida. MATERIALS AND METHODS: Life style questionnaires inquired of knowledge of folic acid in relation to preventing spina bifida during a pregnancy and other relevant parameters, which were collected from 11,861 participants during a period of from 2002 to 2011. Food records asked participants to semi-quantitatively describe diets and beverages they consumed for a 3-day period, which were collected from 1,081 pregnant women from 2003 to 2011. RESULTS: Life style questionnaires demonstrated that knowledge of folic acid and the proportion of those who took folic acid supplements elevated from 15.3 and 9.1% in 2002 to 43.7 and 61.5% in 2011, respectively, that comparison of those who took folic acid supplements from 2008 to 2011 residing in one of 8 districts of Japan showed a significant difference, i.e., the proportion of those in the Chugoku or Kyushu district being significantly lower compared to that in the Hokkaido district, and that other life style parameters have not much altered the past 9 years, e.g., those who conceived as planed being 67%, those who confirmed own pregnancy within 6 weeks of pregnancy being 70%, those who took balanced diets being 65%, and those who did not smoke or drink being 95% and 96%, respectively. Three-day food records revealed that the mean dietary folate intakes ranged from 260 to 360 microg/day in each year which were less than the recommended dietary allowance (RDA) publicized by the government, but that the proportion of pregnant women in the first trimester who consumed folic acid supplements from 4 weeks prior to to 12 weeks after conception increased from 7.4% in 2003 to 69.6% in 2011. CONCLUSIONS: As a whole it could be stated that life styles of pregnant women have been shifting toward the direction the past 10 years where the risk for having a pregnancy afflicted with spina bifida is to be decreased. Medical doctors, nurses, midwives, dietitians and pharmacists are asked to repeatedly supply important information on folic acid and to advise taking folic acid supplements 400 microg a day to women planning to conceive or women in the reproductive age.

Dietary folate intakes and effects of folic acid supplementation on folate concentrations among Japanese pregnant women.

AIM: To quantify the consumed amount of dietary folate and to evaluate effects of folic acid and balanced diets on serum folate concentrations. MATERIAL & METHODS: Food records collected from 641 pregnant women were assessed to quantify the consumed amount of dietary folate for a 6-year period from 2003 to 2008. Changes in serum folate concentrations were evaluated among 80 pregnant women who either took folic acid tablets or consumed balanced diets in 2008. RESULTS: Though the dietary folate intake averaged 331 µg daily, 200 women in the 1st trimester consumed the least amount of dietary folate, 294 µg daily. It was observed that 42% of the 200 women either consumed at least 440 µg of dietary folate daily or took 400 µg folic acid supplements daily, but that 58% of them neither consumed dietary folate of 440 µg nor took folic acid supplements. Intakes of 400 µg folic acid supplements for 5 weeks resulted in a significant increase in serum folate concentrations but the consumption of balanced diets had no effect on increasing folate concentrations. CONCLUSIONS: The average intake of dietary folate did not fulfill the Recommended Dietary Allowance of 440 µg. Serum folate concentration significantly increased only among pregnant women who took folic acid supplements. Recommendations to consume balanced diets do not seem effective to decrease the incidence of neural tube defects.

Folic acid in the prevention of neural tube defects: awareness among laywomen and healthcare providers in Japan.

It is known that neural tube defects are folic acid preventable congenital anomalies. We investigated to what extent this information was disseminated among laywomen and healthcare providers. Questionnaire studies were conducted twice, in 2002 and 2007, for four groups of laywomen and seven groups of healthcare providers in Japan regarding awareness, folic acid supplements and healthy diets. Awareness among laywomen was less than 20%, except for families who had experience with spina bifida in 2002, and 5 years later only pregnant women showed a significant increase in awareness. Awareness among healthcare providers varied from 12 to 76%, depending on their profession, and this proportion increased in five of the seven groups in 2007. The majority of laywomen obtained their information from mass media, while the majority of healthcare providers received information through media for professionals. Laywomen who used folate supplements and healthcare providers who recommended them were initially fewer than 25 and 37%, respectively. Five years later, however, pregnant women who used folic acid supplements increased from 9.1 to 43.1%. As awareness among non-pregnant laywomen and some healthcare providers is considerably low, information should be presented repeatedly to these groups. The difficulty in getting women to consume folic acid supplements is an argument for the government to require folic acid fortification of grains so that the prevention of neural tube defects can be maximized.

Neural tube defects: prevalence, etiology and prevention.

Spina bifida and anencephaly, the common form of neural tube defects, affect approximately 300 000 newborns each year worldwide. The effectiveness of folic acid supplementation in preventing their occurrence or recurrence has been unambiguous since 1991. In general, the prevalence of these abnormalities has decreased in the past 20 to 30 years because of periconceptional folate supplementation, food fortification in several countries, avoiding exposure to environmental factors, and increased accuracy of prenatal screening for fetal anomalies. Women who are planning to conceive should be informed about the importance of folic acid in fetal development and advised to take 400 microg/day of folic acid supplements. Food fortification with folic acid will ultimately be necessary to reduce the number of patients. Primary prevention of neural tube defects by the periconceptional intake of folic acid is a major public health opportunity and has wide implications in reducing the mortality and morbidity of offspring.

[Folic acid reduces the risk of neural tube defects: awareness and folate intake among pregnant women in 2006].

Folic acid plays an important role in proliferating cells and tissues of the fetus. A randomized control trial demonstrated in 1991 that 4 mg of folic acid supplements successfully prevented 72% of recurrence of neural tube defects (NTDs) in women who had had afflicted pregnancy. In 2000, the Japanese Government recommended women of childbearing age to take 400 microgram of folate supplements per day from 4 weeks prior to and 12 weeks after conception. A questionnaire study was performed in pregnant women by post on their awareness of the role folic acid plays, their life style, and folate intake by dietary consumption. Thirty-five percent of 1,251 pregnant women were aware of the important role of folic acid in the critical stage of fetal development and 31% actually took the supplement. Information on folic acid was obtained through mass media in 47% of the women, through the internet in 17%, through healthcare providers in 13% and so forth. The food record analysis revealed that the dietary intake of folic acid averaged 341 microg/day that was 60 microg less than what was recommended by the Government and that 33 of 86 women took the supplement. Overall, a half of pregnant women are required to take 400 microg folate supplement per day. It is to be stressed that primary prevention of NTDs by periconceptional intake of folic acid is a major public health opportunity and that prevention is more important than cure in the management of NTDs.

[Periconceptional intake of folate reduces the risk of neural tube defects: awareness among urologists in 2007].

AIMS: Folic acid is one of water-soluble Vitamin B group and plays an important role in proliferating cells of the fetus. A multicentered, randomized control trial proved in 1991 that folic acid supplements of 4 mg per day periconceptionally administered to 1031 women who were recruited from 7 countries and had afflicted prior pregnancy successfully prevented 72% of recurrence of neural tube defects. As a primary prevention method, the Government has recommended to take 400 microgram of folate supplements per day from 4 weeks before and 12 weeks after conception. Because of huge amount of folate being demanded in the first trimester, this vitamin is called as "vitamin for women" or "vitamin for fetuses". We herewith report results of questionnaire study performed among urologists. MATERIALS AND METHODS: A questionnaire was sent July 2007 to 400 urologists randomly selected from the Membership Directory of the Japanese Urological Association 2006 whether they are aware of the role of folic acid and how they guide young women or pregnant women on their life style. One hundred sixty-one responses were obtained (40%). RESULTS: Thirty-six percent of urologists were aware of the important role of folic acid in the critical stage of fetal development, which was significantly elevated compared to 26% observed in 2002 (p = 0.037). Fifty-seven percent of urologists acquired this information through Japanese Urological Association or medical journals, 17% through mass media, and 7% through internet. Those who guided young women or pregnant women to refrain from smoking, to abstain from alcohol, to take well-balanced meals and to take folate supplements were 73%, 62%, 67% and 7%, respectively. Ninety-two percent of urologists agreed to provide this information to young women or pregnant women. CONCLUSION: Birth incidence of spina bifida has been increasing in Japan. In order to suppress incidence of this congenital anomaly, Urologists are requested to send young women a message that maternal periconceptional intake of folate will suppress the risk of congenital anomalies.

[Efficacy and safety of propiverine on improvement of symptoms and QOL for female patients with wet overactive bladder].

The present study was prospectively conducted for female patients with wet overactive bladder to assess the efficacy of propiverine hydrochloride in improving their symptoms and quality of life (QOL). Propiverine hydrochloride was administered orally to 58 patients for 8 weeks. Prior to administration and at 4 and 8 weeks after administration, symptoms and QOL were assessed by the micturition diary, the International Consultation on Incontinence-Short Form (ICIQ-SF), and the King's Health Questionnaire (KHQ). After administration, numbers of daily micturitions, incontinence episodes, urgency episodes and severity of urgency which were assessed based on the micturition diary and urgency scale questionnaire showed significant improvement when compared to baseline values. Furthermore, both ICIQ-SF and KHQ scores improved significantly after administration. The incidence of adverse events was 23.8% and none were serious. Propiverine hydrochloride was shown to contribute not only to the improvement of symptoms in female patients with wet overactive bladder but also to their QOL.

Folic acid prevents neural tube defects: international comparison of awareness among obstetricians/gynecologists and urologists.

AIM: It has been suggested that periconceptional intake of folic acid prevents risks of having fetuses afflicted with neural tube defects. We aim to internationally investigate knowledge of the role of folic acid and attitudes toward the life-style of young women of child-bearing age among obstetricians/gynecologists and urologists. METHODS: A questionnaire was sent to obstetricians/gynecologists and urologists residing in Japan, South Korea, Taiwan, North America, Europe, Australia and New Zealand by post or e-mail. The investigation was conducted between December 2002 and November 2004. RESULTS: A mean of 91% of obstetricians/gynecologists and 56% of urologists are aware of the role of folic acid, where Asian urologists knew less compared to those of North America, Europe, Australia and New Zealand. A majority of doctors always, or occasionally, recommend folic acid supplements or multivitamins, well-balanced meals, and the cessation of smoking and drinking. An average of 85% of doctors believes information on folic acid should be disseminated to young women. CONCLUSIONS: A majority of obstetricians/gynecologists and urologists know the importance of periconceptional folic acid in reducing the risk of neural tube defects and have been advising young women to improve their lifestyle.

Efficacy, safety and hospital costs of tension-free vaginal tape and pubovaginal sling in the surgical treatment of stress incontinence.

AIM: The efficacy, safety and hospital costs of the tension-free vaginal tape procedure were compared with the pubovaginal sling operation. METHODS: A total of 60 women urodynamically diagnosed as having stress or mixed urinary incontinence were operated on using either the tension-free vaginal tape or pubovaginal sling operation in a prospective manner. Preoperative characteristics of the women were not significantly different for the groups. The women were followed for up to 24 months. RESULTS: In the tension-free vaginal tape group, the operation time was shorter, numbers of analgesics postoperatively required were less and hospital charges were less expensive compared to those in the pubovaginal sling operation (P < 0.01). Kaplan-Meier survival analysis showed a marginal significant difference (P = 0.059) in the objective cumulative cure rates at 24 months between the groups receiving the former (70.3%) and latter (48.3%) procedures. Subjective cure rates were not significantly different (P = 0.101). In both groups, an improvement in quality of life was significant and surgical complications were identical. De novo urge incontinence developed in 6% and 10% in the former and latter, respectively. CONCLUSIONS: The tension-free tape was significantly superior to the pubovaginal sling in terms of operation time, postoperative pain, and hospital charges, but not in cure rates. A longer follow up with a larger sample size is necessary to draw definite conclusions.